Method for production of isocyanates

ABSTRACT

In a process for preparing isocyanates by reacting the corresponding primary amines with phosgene in an inert solvent, use is made of from 0.01 to 50 mol % of a sulfonamide, based on the total amount of primary amine and isocyanate formed in the reaction solution.

This application is filed under 35 USC 371 and claims the benefit ofPCT/EP02/11624, filed Oct. 17, 2002.

The present invention relates to an improved process for preparingisocyanates by reacting the corresponding primary amines with phosgenein an inert solvent.

Isocyanates are large-scale industrial products having many uses in thefield of polyurethane polymers. However, some isocyanates are alsoemployed in the preparation of pharmaceutically active compounds.

The synthesis of isocyanates by reaction of amines with phosgene hasbeen known for a long time. Two basic processes are described in theliterature, of which one is carried out at atmospheric pressure and theother is carried out under superatmospheric pressure. The phosgenationunder superatmospheric pressure has the disadvantage that it requires agreatly increased outlay in terms of apparatus to cope with theincreased safety risk, namely the escape of phosgene.

A process for preparing sulfonyl isocyanates at atmospheric pressure, inwhich a solution of a sulfonyl amide and an isocyanate as catalyst isreacted with phosgene in an inert solvent, is known from U.S. Pat. No.3,371,114 and U.S. Pat. No. 3,484,466. In this process, thecorresponding sulfonylurea is formed as an intermediate and reacts withphosgene to form the desired sulfonyl isocyanate.

Alkyl and aryl isocyanates are usually prepared from the correspondingamines in two stages at atmospheric pressure by the phosgenationprocesses described, for example, in Ullmann's Encyclopedia ofIndustrial Chemistry, 6^(th) edition, 2000 electronic release, Chapter“ISOCYANATES, ORGANIC—Production”. In the first stage, the coldphosgenation, the amine is reacted with an excess of phosgene in highlydilute solution and reacted at low temperatures to form thecorresponding carbamoyl chloride from which the isocyanate is formed inthe second stage at elevated temperature, viz. the hot phosgenation.Owing to their increased basicity compared to aromatic amines, aliphaticand cycloaliphatic primary amines are more difficult to phosgenate andlead to increased formation of by-products. Disadvantages of theseprocesses are the need to carry out the phosgenation in two stages andalso, in particular, the formation of an intermediate suspension ofsparingly soluble carbamoyl chloride and amine hydrochloride which inturn makes increased dilution of the reaction medium necessary toprevent deposits on and blockages of plant components. Owing to thesolid formed, this process cannot be carried out continuously atatmospheric pressure. Furthermore, the process results in formation of asymmetrically N,N′-disubstituted urea as by-product, and the formationof this can only be suppressed at the cost of drastically reducedspace-time yields.

Aliphatic and cycloaliphatic amines are frequently used in the form oftheir salts in the cold/hot phosgenation. However, these salts aresparingly soluble in the reaction medium, so that additional reactionsteps and very long reaction times become necessary.

Furthermore, U.S. Pat. No. 3,440,268 and U.S. Pat. No. 3,492,331 teachthe reaction of primary amines with phosgene in the presence of anN,N-disubstituted formamide, an N-alkyllactam, an N,N-disubstitutedN′-arylformamidine or an N,N,N′,N′-tetrasubstituted N″-arylguanidine ascatalyst. H. Ulrich, Chemistry & Technology of Isocyanates, Wiley &Sons, 1996, pages 328 to 330, discloses the reaction of primary amineswith phosgene in the presence of tertiary amines, tetramethylurea andcarbonyldiimidazole as catalyst, and CS 262 295 discloses the use ofN,N′-diazabicyclo[2.2.2]octane as catalyst. Some of the compoundsspecified have to be used in equimolar amounts and form sparinglysoluble salts in the form of the catalyst hydrochloride adducts underthe reaction conditions. Furthermore, the amine used and the hydrogenchloride formed react to produce sparingly soluble amine hydrochloride.

WO 01/17951 teaches the preparation of isocyanates by phosgenation ofthe corresponding primary amines in the presence of a monoisocyanatewhich is initially charged in an inert solvent prior to commencement ofthe reaction and is admixed with phosgene. A disadvantage of thisprocess is that the preferred low molecular weight aliphatic isocyanatesare toxic and require strict safety precautions.

It is an object of the present invention to find a process for preparingisocyanates which no longer has the above-mentioned disadvantages, canbe carried out both continuously and batchwise, displays no formation oronly insignificant formation of sparingly soluble components, can becarried out without a highly toxic catalyst, makes it possible for thereaction to be carried out in only one reaction stage and leads to ahigh conversion, a high selectivity and a high space-time yield evenunder mild temperature and pressure conditions.

We have found that this object is achieved by a process for preparingisocyanates by reacting the corresponding primary amines with phosgenein an inert solvent, wherein from 0.01 to 50 mol % of a sulfonamide,based on the total amount of primary amine and isocyanate formed in thereaction solution, is used.

The sulfonamide which can be used in the process of the presentinvention has the formula (I)R¹—SO₂—NH₂  (I),where the radical R¹ is a carbon-containing organic radical.

For the purpose of the present invention, a carbon-containing organicradical is an unsubstituted or substituted, aliphatic, aromatic oraraliphatic radical. This may contain one or more heteroatoms such asoxygen, nitrogen, sulfur or phosphorus, for example —O—, —S—, —NR—,—CO—, —N═, —SiR₂—, —PR— and/or —PR₂, and/or be substituted by one ormore functional groups which contain, for example, oxygen, nitrogen,sulfur and/or halogen, for example by fluorine, chlorine, bromine,iodine and/or a cyano group (the radical R is likewise acarbon-containing organic radical). The carbon-containing organicradical can be a monovalent radical or else a divalent or trivalentradical.

The radical R¹ is preferably

-   -   an unbranched or branched, acyclic or cyclic, unsubstituted or        substituted alkyl radical which has from 1 to 30 aliphatic        carbon atoms and in which one or more of the CH₂ groups may be        replaced by heteroatoms such as —O— or —S— or by        heteroatom-containing groups such as —CO—, —NR— or —SiR₂—, and        in which one or more of the hydrogen atoms may be replaced by        substituents such as aryl groups or functional groups; or    -   an unsubstituted or substituted aromatic radical which has from        3 to 30 carbon atoms and one ring or two or three fused rings        and in which one or more ring atoms may be replaced by        heteroatoms such as nitrogen and in which one or more of the        hydrogen atoms may be replaced by substituents such as alkyl or        aryl groups or functional groups.

Particular preference is given to using sulfonamides (I) whose radicalR¹ is

-   -   an unbranched or branched C₁–C₂₀-alkyl radical such as methyl,        ethyl, 1-propyl, 2-propyl (sec-propyl), 1-butyl, 2-butyl        (sec-butyl), 2-methyl-1-propyl (isobutyl), 2-methyl-2-propyl        (tert-butyl), 1-pentyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl        (tert-amyl), 1-hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl,        3-methyl-3-pentyl or 2-methoxy-2-propyl;    -   an unbranched or branched C₅–C₂₀-cycloalkyl radical such as        cyclopentyl, cyclohexyl or cyclooctyl; or    -   a C₆–C₂₀-aryl or C₃–C₂₀-heteroaryl radical which may be        unsubstituted or substituted by one or more C₁–C₄-alkyl        radicals, for example phenyl, 2-methylphenyl (o-tolyl),        3-methylphenyl (m-tolyl), 4-methylphenyl (p-tolyl),        2,6-dimethylphenyl, 2,4-dimethylphenyl, 2,4,6-trimethylphenyl,        2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-pyridyl,        3-pyridyl, 4-pyridyl, 3-pyridazinyl, 4-pyridazinyl,        5-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,        2-pyrazinyl, 2-(1,3,5-triazin)yl, 1-naphthyl, 2-naphthyl,        2-quinolyl, 8-quinolyl, 1-isoquinolyl or 8-isoquinolyl.

Very particular preference is given to using sulfonamides (I) whoseradical R¹ is

-   -   an unbranched or branched C₁–C₁₀-alkyl radical;    -   an unbranched or branched C₅–C₁₀-cycloalkyl radical; or    -   a C₆–C₁₂-aryl radical which may be unsubstituted or substituted        by one or more C₁–C₄-alkyl radicals.

In particular an aromatic sulfonamide, very particularly preferablyp-toluenesulfonamide, is used in the process of the present invention.

The sulfonamide is used in a catalytic amount of from 0.01 to 50 mol %,based on the total amount of primary amine and isocyanate formed in thereaction solution. In calculating the total amount of primary amine andisocyanate formed, the molar amounts of the not yet reacted startingmaterial (primary amine) and the product which has been formed(isocyanate) and any intermediates present are to be added. In theprocess of the present invention, preference is given to using from 0.01to 25 mol %, particularly preferably from 0.5 to 20 mol % and veryparticularly preferably from 1 to 15 mol %, of sulfonamide, based on thetotal amount of primary amine and isocyanate formed in the reactionsolution.

In the process of the present invention, the sulfonamide is generallyinitially charged in an inert solvent. For the purposes of the presentinvention, inert solvents are solvents which are chemically inert towardthe primary amine used, the phosgene, the isocyanate formed and thesulfonamide used. “Chemically inert” means that the diluents do notreact chemically with the substances mentioned under the chosenconditions. Preference is given to using aromatic or aliphatichydrocarbons, particularly preferably monosubstituted or polysubstitutedaromatic hydrocarbons such as toluene, o-, m-, p-xylene, ethylbenzene,chlorobenzene or o-, m-, p-dichlorobenzene. Very particular preferenceis given to o-, m- or p-xylene, chlorobenzene, o-, m-, p-dichlorobenzeneand mixtures thereof.

In general, the introduction of phosgene is then commenced. It can beintroduced in liquid or gaseous form. It is usual for from about 10 to50% of the theoretically required amount of phosgene, based on thereaction volume, to be introduced initially.

Addition of the primary amine to the phosgene-laden starting solution ofsulfonamide in the inert solvent is then commenced. Further phosgene isintroduced in accordance with the progress of the reaction and theamount of amine added.

The primary amines which can be used in the process of the presentinvention have the formula (II)R²—NH₂  (II),where the radical R² is a carbon-containing organic radical as definedabove.

The radical R² is preferably

-   -   an unbranched or branched, acyclic or cyclic, unsubstituted or        substituted alkyl radical which has from 1 to 30 aliphatic        carbon atoms and in which one or more of the CH₂ groups may be        replaced by heteroatoms such as —O—, or —S— or by        heteroatom-containing groups such as —CO—, —NR— or —SiR₂— and in        which one or more of the hydrogen atoms may be replaced by        substituents such as aryl groups or functional groups, with the        exception of —OH, —SH and —COOH groups; or    -   an unsubstituted or substituted aromatic radical which has 3 to        30 carbon atoms and one ring or two or three fused rings and in        which one or more ring atoms may be replaced by heteroatoms such        as nitrogen and in which one or more of the hydrogen atoms may        be replaced by substituents such as alkyl or aryl groups or        functional groups, with the exception of —OH, —SH and —COOH        groups.

In particular, the radical R² may bear one or more further NH₂ groups,so that oligoamines having two or more NH₂ groups are explicitlyincluded as primary amines. The primary amine used is particularlypreferably a monoamine having one NH₂ group or a diamine having two NH₂groups, each having from 1 to 20 carbon atoms.

As examples of suitable acyclic and substituted or unsubstituted alkylradicals R², mention may be made of methyl, ethyl, 1-propyl, 2-propyl(sec-propyl), 1-butyl, 2-butyl (sec-butyl), 2-methyl-1-propyl(isobutyl), 2-methyl-2-propyl (tert-butyl), 1-pentyl, 2-pentyl,3-pentyl, 2-methyl-2-butyl (tert-amyl), 1-hexyl, 2-hexyl, 3-hexyl,2-methyl-2-pentyl, 3-methyl-3-pentyl, 1-octyl, 1-decyl, 2-aminoethyl,3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 8-aminooctyl,phenylmethyl, 1-phenylethyl, 1-phenylpropyl or 1-phenylbutyl.

As examples of cyclic and substituted or unsubstituted cycloalkylradicals R², mention may be made of cyclopentyl, cyclohexyl, cyclooctylor 3-aminomethyl-3,5,5-trimethylcyclohexyl.

As examples of aromatic and heteroaromatic and substituted orunsubstituted radicals R², mention may be made of phenyl, o-, m-,p-tolyl and aminotolyls.

It may be emphasized that enantiomerically pure, optically activecompounds or mixtures thereof having an optically active carbon bound tothe NH₂ group can also be used as primary amines. Advantageously, theprocess of the present invention leads to only a small degree ofracemization, generally below 2%, during the reaction and the work-up.

The primary amine used in the process of the present invention is veryparticularly preferably 1,6-diaminohexane, cyclohexylamine,isophoronediamine (3-aminomethyl-3,5,5-trimethylcyclohexylamine),aniline, a diaminotoluene, diphenylmethane-4,4-diamine, R-(+)- andS(−)-phenylethylamine.

The molar ratio of the total amount of phosgene introduced to theprimary amine groups to be phosgenated is generally from 1 to 10,preferably from 1 to 5 and particularly preferably from 1 to 2, inparticular from 1.2 to 1.8.

The amount of inert solvent is generally from 100 to 2000% by weight andpreferably from 300 to 1000% by weight, based on the total amount of theprimary amine present and the isocyanate formed.

The process of the present invention is generally carried out at from 20to 200° C., preferably from 20 to 150° C. and particularly preferablyfrom 50 to 100° C. In carrying out the process of the present invention,the pressure is generally from 0.05 to 0.5 MPa abs and-preferably from0.08 to 0.12 MPa abs.

After the desired amount of phosgene and amine has been added, thereaction solution obtained is generally left for a certain time, ingeneral from 30 minutes to 6 hours, under the reaction conditions toallow further reaction to occur. To remove or reduce the amount ofexcess phosgene and its reaction products carbon dioxide and hydrogenchloride from/in the reaction solution, it is usual for inert gassubsequently to be passed through the mixture with intensive mixing(“stripping”).

The process of the present invention can in principle be carried outeither continuously or batchwise, with continuous operation beingpreferred. The process can be carried out in any apparatus suitable fora reaction with phosgene. Suitable reactors are, for example, stirredvessels.

The reaction mixture after the reaction is generally worked up by knownmethods. Preference is given to isolating the desired isocyanate byfractional distillation. The sulfonamide used as catalyst is preferablyrecovered by distillation and, in the case of a continuous process,recirculated.

In a general embodiment for the batchwise preparation of isocyanates,the sulfonamide together with an inert solvent are placed while stirringin a reactor, for example a stirred vessel, and the solution is loadedwith phosgene. The reaction system is then brought to the desiredtemperature and the introduction of the amine is commenced. Furtherphosgene is introduced in accordance with the progress of the reactionand the amount of amine fed in. After the desired amount of phosgene hasbeen fed in, the reaction solution is left at the set temperature forsome time while continuing to stir to allow further reaction to occur.

During this after-reaction time, phosgene which is still present in thereaction solution reacts with residual amine. To remove or reduce theconcentration of the excess phosgene and its reaction products carbondioxide and hydrogen chloride from/in the reaction solution, it ispossible to pass inert gas through the mixture while mixing intensively(“stripping”). The reaction solution obtained is then passed to work-up.In general, the work-up is carried out by distillation, if appropriateunder reduced pressure. In the case of relatively high-boilingisocyanates, other purification methods, for example crystallization,are also possible.

In a general embodiment for the continuous preparation of isocyanates,the sulfonamide together with an inert solvent are placed while stirringin the reactor, for example a stirred vessel, and the solution is loadedwith phosgene. The reaction system is then brought to the desiredtemperature and the continuous introduction of the amine is commenced.Further phosgene is introduced continuously in accordance with theprogress of the reaction and the amount of amine fed in. After thecontents of the reactor have largely reacted to form isocyanate, theamounts of amine and phosgene are adjusted so that both are addedessentially in the stoichiometric required ratio. An amount of thereaction solution corresponding to the amount fed in is taken from thereaction apparatus, for example via a level regulator or an overflow.The reaction solution which has been taken off is collected in adownstream container, for example a stirred vessel, to allow furtherreaction to occur. After the downstream container has been filled by thereaction mixture, the overflow is, if appropriate, freed of thecoproducts carbon dioxide and hydrogen chloride by stripping asdescribed above and is passed to work-up. The work-up can be carriedout, for example, by distillation.

The process of the present invention makes it possible to prepareisocyanates by continuous or batchwise phosgenation of primary amines.Compared to known, catalyst-free processes, it makes it possible tocarry out the actual reaction in only a single reaction stage under mildtemperature and pressure conditions, and gives a higher conversion ofprimary amine, a high selectivity and a high space-time yield ofisocyanate. Compared to the known, catalyst-free processes and the knownprocesses in the presence of a catalyst, the process of the presentinvention has no tendency, or only an insignificant tendency, to formsparingly soluble components. The risk of deposits on and blockages ofplant components is significantly reduced thereby, which represents adecisive safety advantage when handling toxic phosgene. Furthermore, thenonformation or only insignificant formation of sparingly solublecomponents makes it possible to carry out a continuous process for thefirst time and gives significant advantages in the subsequent work-up.

The sulfonamides used in the process of the present invention aregenerally nontoxic or have only a low toxicity, which represents, inparticular, an advantage over the use of an aliphatic monoisocyanatedescribed in WO 01/17951.

EXAMPLES Experimental Apparatus

The experimental apparatus comprised a 1 glass vessel provided with astirrer, a thermostat, an inlet tube for the gaseous phosgene and atwo-part condenser cascade. The two-part condenser cascade comprises anintensive condenser which was maintained at −10° C. and a carbon dioxidecondenser which was maintained at −78° C. The experiments were carriedout at atmospheric pressure.

Comparative Example 1

500 g of chlorobenzene were placed in the glass vessel and 40 g ofgaseous phosgene was introduced at room temperature. The reactionmixture was subsequently heated to 77° C., with vigorous phosgene refluxbeing established. While stirring vigorously at 77–80° C., a total of99.2 g of cyclohexylamine (1 mol) dissolved in 200 g of chlorobenzeneand at the same time a further 92 g of phosgene were introduced over aperiod of 3 hours. After addition was complete, the system wasmaintained at 77–80° C. for a further one hour without introduction ofphosgene to allow further reaction to occur and the residual unreactedphosgene was subsequently stripped out at 50° C. by means of nitrogen.The reaction mixture obtained was a suspension from which the solidobtained was separated by filtration. 15 g of solid which, according toIR-spectroscopic analysis, was mainly amine hydrochloride were able tobe isolated in this way. The filtered crude product was worked up bydistillation. Removal of the solvent and fractional distillation gave88.8 g of cyclohexyl isocyanate (0.710 mol). This corresponds to 71.0%of the theoretical yield.

Example 2 According to the Present Invention

500 g of chlorobenzene and 4.3 g of p-toluenesulfonamide (0.025 mol)were placed in the glass vessel and 33 g of gaseous phosgene wasintroduced at room temperature. The reaction mixture was subsequentlyheated to 79° C., with vigorous phosgene reflux being established. Whilestirring vigorously at 78–81° C., a total of 99.2 g of cyclohexylamine(1 mol) dissolved in 200 g of chlorobenzene and at the same time afurther 122 g of phosgene were introduced over a period of 3 hours.After addition was complete, the system was maintained at 78–81° C. fora further one hour without introduction of phosgene to allow furtherreaction to occur and the residual unreacted phosgene was subsequentlystripped out at 50° C. by means of nitrogen. The reaction mixtureobtained was a fluid suspension from which the solid obtained wasseparated by filtration. <0.5 g of solid was able to be isolated in thisway. Cyclohexyl isocyanate was worked up by distillation. Removal of thesolvent and fractional distillation gave 105.1 g of cyclohexylisocyanate (0.833 mol). This corresponds to 83.3% of the theoreticalyield.

Compared to comparative example 1 without use of a catalyst, example 2according to the present invention using p-toluenesulfonamide displaysonly a very small proportion of solids. Thus, only very little solid hasto be separated off in the process of the present invention.

The significantly lower proportion of solids enables the process of thepresent invention to be carried out significantly more simply, moresafely and with fewer problems. In particular, the risk of deposits onand blockages of plant components is significantly reduced, whichrepresents a decisive safety advantage when handling toxic phosgene andmakes a continuous process possible.

Futhermore, example 2 according to the present invention usingp-toluenesulfonamide displays, at a yield of 83.3% of the theoreticalyield, a considerably higher conversion than comparative example 1without the use of a catalyst, where a yield of 71.0% of the theoreticalyield is obtained.

Compared to the known processes which have to be carried out batchwisebecause of solids formation, the ability to carry out a continuousprocess and to achieve the significantly higher yields enables asignificant increase in the space-time yield to be achieved. Unreactedamine can be returned to the reaction apparatus, so that the achievableyield is considerably higher in the process of the present inventionthan in the known processes.

1. A process for preparing isocyanates which comprises reacting thecorresponding primary amines with phosgene in an inert solvent in thepresence of from 0.01 to 50 mol % of a sulfonamide, based on the totalamount of primary amine and isocyanate formed in the reaction solution.2. A process as claimed in claim 1, wherein the sulfonamide is presentin from 0.01 to 25 mol % based on the total amount of primary amine andisocyanate formed in the reaction solution.
 3. A process as claimed inclaim 1, wherein the sulfonamide is of the formula (I)R¹SO₂NH₂  (I), where the radical R¹ is an unbranched or branchedC₁–C₁₀-alkyl radical, an unbranched or branched C₅–C₁₀-cy-cloalkylradical or a C₆–C₁₂-aryl radical which may be unsubstituted orsubstituted by one or more C₁–C₄-alkyl radicals.
 4. A process as claimedin claim 3, wherein the sulfonamide is p-toluenesulfonamide.
 5. Aprocess as claimed in claim 1, wherein the primary amine is a monoaminehaving one NH₂ group or a diamine having two NH₂ groups, each havingfrom 1 to 20 carbon atoms.
 6. A process as claimed in claim 5, whereinthe primary amine is 1,6-diaminohexane, cyclohexylamine,isophoronediamine, aniline, a diaminotoluene, diphenylmethane4,4′-diamine, R-(+)- or S(−)-phenylethylamine.
 7. A process as claimedin claim 1, wherein the reaction is carried out at from 20 to 200° C.and a pressure of from 0.05 to 0.5 MPa abs.
 8. A process as claimed inclaim 1, wherein the inert solvent is used in an amount of from 100 to2000% by weight, based on the total amount of primary amine present andisocyanate formed.
 9. A process as claimed in claim 1, wherein the inertsolvent is o-, m- or p-xylene, chlorobenzene, o-, m-, p-dichlorobenzeneor a mixture thereof.